ETD

• hap
• hypoxia
• lox
• magl
• monoacylglycerol lipase

The conversion of cells from a normal to cancerous state involves the alteration of several biochemical functions. This progressive change, correlated with malignancy, includes metabolic pathways, but also the instauration of a hostile environment into the cells. Both aggressive and non-aggressive cancer cells necessitate of a lipolytic activity, due to MAGL (Monoacylglycerol lipase), the enzyme which catalyses the hydrolysis of monoglycerols, to liberate glycerol and stored fatty acids. These molecules are precursors of pro-tumorigenic lipid signalling molecules, indispensable to promote migration, survival and tumour growth. In addition, MAGL is involved in the inactivation of 2-arachydonoylglycerol (2-AG), one of the most important endocannabinoids, which seems to have a role as anticancer compounds. For this reason the metabolism of 2-AG, due to MAGL, can promote cancer pathogenesis. Also an unfavourable environment into the cells leads to malignant transformation of tissues. Hypoxia is an oxygen-lacking condition, typical of many cancer diseases, due to the rapid cell growth and the resulting reduced blood flow, in the surrounding tissues. Hypoxia is characterized by an overexpression of LOX (Lysyl Oxidase), an amine oxidase, which provokes the destruction of cell-cell adhesions and the alteration of the extracellular matrix (ECM), to facilitate the tumour invasion and the metastasis. Therefore, LOX and MAGL are important pharmaceutical targets, and the development of their inhibitor may lead to possible anticancer therapies. The aim of this thesis work was the synthesis of prospective inhibitor molecules.